Anticancer Mechanism Of Zicao And Its Active Components

Zicao (Arnebia euchroma (Royle) Johnst), an herbal medicine commonly used in China, is believed to possess properties of removing heat from the blood and detoxification. It has been used for thousands of years for the treatment of macular eruptions, measles, sore-throat, carbuncles and burns. Recent clenical studies have demostrated that Zicao has potent anticancer activity, especially in liver cancer and lung cancer.In this study, we found that Zicao had remarkable inhibitory effect on the growth of lung cancer cell NIH-H460. Intesetingly, co-treatment with 9-cis-RA significantly reversed the action of Zicao in NIH-H460 cells. In vitro ligand binding assay showed that crude Zicao extract contained ingredient(s) to bind RXRα. We further demonstrated that shikonin and its derivates from Zicao could bind RXRα, which was closely related to the inhibition of RXR transactivation by 9-cis-RA. More inportantly, we found the extent of RXR transactivation inhibition by Zicao paralleled with the growth inhibition of NIH-H460 when treated with Zicao. Together, our results strongly suggest the anticancer effect of Zicao is through modulating RXR transactivation.It has been widely showed that Zicao has remarkable anticancer activity; however the molecular mechanisms remain largely unknown. Our findings provide the first evidence that shikonin and its derivatives from Zicao can induce apoptosis in NIH-H460 lung cancer cells by directly binding RXRαand inhibiting RXRαtrasactivation activity, which warrants us to optimize the leads for new drug development.